Bactericidic and fungicidic chloromethylisopropyphenols

ABSTRACT

4-Chloro-3-methyl-2-isopropyl and 4-chloro-3-methyl-5-isopropyl phenols are effective as bactericides and fungicides, especially against staphylococcus, pneumococcus and tricoccus microorganisms in doses as low as 5 parts per million.

This application is a division of Ser. No. 357,812 filed 7 May 1973, nowU.S. Pat. No. 4,098,828 issued 4 July 1978.

FIELD OF THE INVENTION

Our invention relates to bactericidal and fungicidalchloromethylisopropylphenois, to a method of making same and totreatment using these compounds.

OBJECT OF THE INVENTION

The principal object of our invention is to provide efficient andeconomical agents for the treatment of infectious diseases.

Another object of our invention is to provide stable, odorless andnontoxic agents against staphylococcus, pneumococcus, trichomonas andvarious fungus diseases.

DESCRIPTION OF THE INVENTION

We have found that the following chloromethylisopropylphenols havevaluable properties as therapeutic agents, especially for combattingstaphylococcus, pneumococcus, trichomonas and various fungus diseases:

4-chloro-3-methyl-2-isopropyl-phenol (I);

4-chloro-3-methyl-5-isopropyl-phenol (II);

6,6'-methylene-bis (4-chloro-3-methyl-2-isopropyl)-phenol (III); and

2,2'-methylene-bis(4-chloro-3-methyl-5-isopropyl)phenol (IV).

These compounds have the following valuable properties:

They are characterized by surprisingly high bacterocide and fungicideactivity in comparison with similar products;

They are very stable and do not decompose easily; and

They can be obtained in very pure condition, without any toxic byproductor trace compound present, by simple conventional processes.

They can be characterized as follows:

APPEARANCE AND ODOR

I, ii and III: white crystals having a light odor;

Iv: white grains, substantially odor-free.

CHEMICAL NATURE

I and II: 4-chloro-3-methyl-2-isopropyl-phenol and

4-chloro-3-methyl-5-isopropyl-phenol.

Formula Formual C₁₀ H₁₃ ClO

Structural Formula: ##STR1## Molecular Weight: 184.66 ElementalComposition in percent (by weight)

    ______________________________________                                        calculated       C     65.04 H    7.09  Cl   19.19                            found    (I)           65.27      6.93       18.90                                     (II)          65.10      7.15       19.45                            ______________________________________                                    

III and IV: 6,6' methylene-bis(4-chloro-3-methyl-2-isopropyl; and

2,2' methylene-bis(4-chloro-3-methyl-5-isopropyl) phenol.

Empirical Formula: C₂₁ H₂₆ Cl₂ O₂

Structural Formula: ##STR2## Molecular Weight: 381,34 ElementalComposition in percent (by weight):

    ______________________________________                                        calculated       C     66.14 H    6.87  Cl   18.59                            found    (III)         66.39      6.82       18.83                                     (IV)          66.12      6.99       18.51                            ______________________________________                                    

Melting Points: I=52° C.; II=43.5° C., III=130° C.; and IV=175° C.

NUCLEAR MAGNETIC RESONANCE SPECTRUMS

The lines in nuclear magnetic resonance spectrums correspond well withthe proposed formulas as far as position (location) and intensity areconcerned. Their positions are listed in the following Table:

    ______________________________________                                                                     Type of  Multiplet                               Phenol                                                                              Solvent     Protons    Multiplet                                                                              Center                                  ______________________________________                                         I                                                                                   ##STR3##   CH(CH.sub.3).sub.2                                                                       doublet  1.36                                                      CH.sub.3   singulet 2.35                                                      CH(CH.sub.3).sub.2                                                                       septuplet                                                                              3.38                                                      H aromatic quadruplet                                                                             6.84                                                      OH         signal present                                   II                                                                                   ##STR4##   CH(CH.sub.3).sub.2                                                                       doublet  1.17                                                      CH.sub.3   singulet 2.25                                                      CH(CH.sub.3).sub.2                                                                       septuplet                                                                              3.31                                                      H aromatic singulet 6.72                                                      OH         signal present                                   III   CCl.sub.4   CH(CH.sub.3).sub.2                                                                       doublet  1.32                                                      CH.sub.3   singulet 2.31                                                      CH(CH.sub.3).sub.2                                                                       septuplet                                                                              3.35                                                      CH.sub.2   singulet 3.70                                                      OH         singulet 5.6                                                       H aromatic singulet 7                                       IV    CDCL.sub.3  CH(CH.sub.3).sub.2                                                                       doublet  1.14                                                      CH.sub.3   singulet 2.40                                                      CH(CH.sub.3).sub.2                                                                       septuplet                                                                              3.38                                                      CH.sub.2   singulet 4.05                                                      H aromatic singulet 6.63                                                      OH         singulet 6.63                                    ______________________________________                                    

EXAMPLE I 4-chloro-3-methyl-2-isopropyl-phenol and4-chloro-3-methyl-5-isopropyl-phenol

135 g sulfurylchloride is added slowly to 150 g phenolic base and areaction takes place at 60°-90° C. When the addition is terminated, thereaction mixture is neutralized with normal caustic potash. Theresulting phenolic phase is decanted and washed with distilled water.

The chlorination in this manner of 3-methyl-2-isopropyl-phenol gives 170g raw product containing approximately 50% by weight of compound I. Thisraw product can be recovered by distillation and recrystallized inpetroleum ether to yield 60 g of pure compound I with a melting point of52° C. The yield is 32%.

The chlorination of 3-methyl-5-isopropyl-phenol gives 175 g raw productcontaining approximately 75% by weight of compound II. This raw productis distilled and recrystallized in petroleum ether. The yield is 80 g ofII, which is pure and melts at 43.5°C. The yield is 43%.

EXAMPLE 6.6'-methylene-bis(4-chloro-4-methyl-2-isopropyl)phenol and2.2'-methylene-bis(4-chloro-3-methyl-2-isopropyl)phenol.

6.6 g caustic potash is added to 184.6 g of compound I, then 314 gisopropyl alcohol; this mixture is heated to 45° C. and 42 g of36%-formaldehyde are added. This mixture is maintained at 45° C. andagitated for six hours and then cooled to ambient temperature. Thepotash is neutralized with 20 g diluted hydrochloric acid and 550 g ofpetroleum ether are added.

The resulting water phase is decanted and the solvent is completelyevaporated. The residue is a brown sticky mass, 190 g, which isredissolved in petroleum ether. Recrystallization gives 75 g of purecompound III, which is a satisfactory yield of 38%.

Compound IV can be prepared in the same manner. The yield is 30%.

The compounds I-IV have excellent therapeutic properties. They can beused for treating infections caused by staphylococcus, pneumococcus andtrichomonas and mycosis, e.g. candidosis. They are administered as watersolutions by local or topical application, having very lowconcentrations of the compounds (approximately 5 ppm) and are then mosteffective and, in addition, are totally nontoxic.

The compounds can be generally described by the formula: ##STR5## wherethe members R₁, R₂ and R₃ are each hydrogen, isopropyl ormethylenechloromethylisopropylphenol and at least one of the members R₁,R₂ or R₃ is isopropyl.

We claim:
 1. A chloromethylisopropylphenol selected from the group whichconsists of 4-chloro-3-methyl-2-isopropyl-phenol and4-chloro-3-methyl-5-isopropyl-phenol.
 2. The chloromethylisopropylphenoldefined in claim 1 which consists of4-chloro-3-methyl-2-isopropyl-phenol.
 3. The chloromethylisopropylphenoldefined in claim 1 which consists of4-chloro-3-methyl-5-isopropyl-phenol.